Abstract
Rationale
Atypical attention orienting has been associated with some autistic symptoms, but the neural mechanisms remain unclear. The human Posner task, a classic attention orienting paradigm, was recently adapted for use with mice, supporting the investigation of the neurobiological underpinnings of atypical attention orienting in preclinical mouse models.
Objective
The current study tested mice expressing the autism-associated R451C gene mutation in neuroligin-3 (NL3) on the mouse-Posner (mPosner) task.
Methods
NL3R451C and wild-type (WT) mice were trained to respond to a validly or invalidly cued target on a touchscreen. The cue was a peripheral non-predictive flash in the exogenous task and a central spatially predictive image in the endogenous task. The effects of dopaminergic- and noradrenergic-modulating drugs, methylphenidate and atomoxetine, on task performance were assessed.
Results
In both tasks, mice were quicker and more accurate in the validly versus invalidly cued trials, consistent with results in the human Posner task. NL3R451C and WT mice showed similar response times and accuracy but responded differently when treated with methylphenidate and atomoxetine. Methylphenidate impaired exogenous attention disengagement in NL3R451C mice but did not significantly affect WT mice. Atomoxetine impaired endogenous orienting in WT mice but did not significantly affect NL3R451C mice.
Conclusions
NL3R451C mice demonstrated intact attention orienting but altered responses to the pharmacological manipulation of the dopaminergic and noradrenergic networks. These findings expand our understanding of the NL3R451C mutation by suggesting that this mutation may lead to selective alterations in attentional processes.
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Data Availability
The data that support the findings of this study are available from the corresponding authors upon reasonable request.
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Acknowledgements
We thank Maddison Ible, Daniel Drieberg, and Brett Purcell for mouse husbandry and management of equipment. We are also grateful to our laboratory members for helpful discussions and technical support.
Funding
SL is supported by the Melbourne Research Scholarship established by the University of Melbourne. ELB is supported by a National Health and Medical Research Council-Australian Research Council (NHMRC-ARC) Dementia Research Development Fellowship (1111552) and funding from TDM Growth Partners and Hearts and Minds Investments. AJH is a National Health and Medical Research Council (NHMRC) Principal Research Fellow and has been supported by an Australian Research Council (ARC) FT3 Future Fellowship (FT100100835).
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SL, KAJ, and ELB conceived and designed the study. SL and ELB carried out the experiments with assistance from TYP. SL analysed the data with statistical advice from CM, LC, and ELB. SL, KAJ, and ELB contributed to the interpretation of the results. SL wrote the manuscript with input from KAJ, ELB, LC, TYP, and AJH. All authors read the final version and consented to publishing this manuscript.
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Katherine A. Johnson and Emma L. Burrows are joint senior authors.
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Li, S., May, C., Pang, T.Y. et al. Mice with an autism-associated R451C mutation in neuroligin-3 show intact attention orienting but atypical responses to methylphenidate and atomoxetine in the mouse-Posner task. Psychopharmacology 241, 555–567 (2024). https://doi.org/10.1007/s00213-023-06520-6
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DOI: https://doi.org/10.1007/s00213-023-06520-6